Rats reduce intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse such as morphine or cocaine. This reduction in CS intake has led to the long standing assumption that drugs of abuse induce conditioned taste aversions via aversive properties. Papers published over the last funding period, however, argue against this account in support of the alternative hypothesis that rats avoid intake of the saccharin CS because they are anticipating the rewarding properties of the drug. Thus, published data now show that the suppressive effects of a rewarding sucrose solution, morphine, and cocaine, but not those of the aversive agent, LiCI, are similarly affected by the value of the CS, the deprivation state of the rat, the strain of the rat, a history of chronic morphine treatment, bilateral lesions of the gustatory thalamus, bilateral lesions of the gustatory cortex and, according to new preliminary data, unilateral asymmetric lesions of the gustatory thalamus and cortex. Lesions of the ventral tegmental area are without effect, but microdialysis data showed that accumbens dopamine clearly tracks drug-induced devaluation of the saccharin reward cue. Specific Aim 1 uses asymmetric lesions to test whether the suppressive effects of drugs and sweets, but not those of the aversive agent, LiCI, depend upon communication between the gustatory thalamus and cortex. Specific Aim 2 tests whether the lesion-induced disruption in cocaine suppression is mediated by the same selective memory/reward comparison deficit found with sucrose suppression. Finally, Specific Aim 3 tests whether accumbens dopamine depends upon an intact thalamocortical loop to track sucrose- and cocaine-, but not LiCI-induced suppression of CS intake. The overarching hypothesis is that this thalamo-cortical loop is required for the comparison of rewards over time, the resulting devaluation of the natural reward, and for the tracking of relative reward properties by the nucleus accumbens. If confirmed, we will have challenged the limits of the traditional "reward circuitry" and better elucidated the mechanisms of reward comparison. [unreadable] [unreadable] [unreadable]